Novel Cognitive and Functional Measure for Alzheimer's Disease Prevention Trials

项目摘要 越来越多的人认识到，实践效应和上限效应可能导致第1类或第2类风险。 考虑到系列评估的必要性，涉及早期AD人群的临床试验中的2型错误。 该提案的总体目标是验证新颖的认知和日常功能测量， 在临床前阿尔茨海默氏症中使用时， 在AD试验中，参与者的认知能力在正常范围内。为了实现这一目标，我们将 一项创新的平行组研究，其中320名健康，非认知障碍的老年受试者， 根据评估类型（新型工具与已建立的工具）随机分为两组，并接受 一年内进行三次连续评估。我们将采用这种平行组设计，以保持 临床试验的结构，同时强调新措施和既定措施之间的对比 完全避免了它们之间的干扰效应。我们新的认知测试包括 执行功能、情景记忆和处理速度组合成一个复合物。我们的功能 这些措施涉及计算机化的基于绩效的、与生态相关的工具活动。我们将 比较我们的新的无练习效应（NPE）认知电池和迈阿密计算机功能 评估量表（CFAS）与包括PACC、ADAS-Cog和FAQ在内的既定措施的对比。在 初步数据我们的新措施表明衰减的实践效果，高重测可靠性， 等效的替代形式，并且缺乏天花板效应。此外，我们还将检查几种生物标志物， 可能增加AD风险的标志物（例如，APOE e4携带状态、海马萎缩和AD皮质 减薄签名，AD家族史），以评估这些已知的测量的敏感性。 生物标志物，并因此提供支持或反对认知和功能测试的有效性的证据。

PROJECT SUMMARY It has become increasingly appreciated that practice effects and ceiling effects could result in type 1 or type 2 errors in clinical trials involving early stage AD populations, given the necessity of serial assessments. This proposal has the overarching goal of validating novel cognitive and everyday functional measures that have sharply attenuated practice effects and are not prone to ceiling effects for use in preclinical Alzheimer's disease (AD) trials in which participants are cognitively within normal limits. To implement this, we will conduct an innovative parallel group study in which 320 healthy, non-cognitively impaired older subjects are randomized to one of two groups based on assessment type (novel instruments vs. established) and receive three serial assessments over a one year period. We will employ this parallel group design in order to maintain the structure of a clinical trial, while pari passu, highlighting contrasts between novel and established measures and completely avoiding any interference effects between them. Our novel cognitive measures include tests of executive function, episodic memory, and processing speed combined into a single composite. Our functional measures involve computerized performance based, ecologically relevant instrumental activities. We will compare our novel No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS) against established measures that include the PACC, ADAS-Cog, and FAQ. In preliminary data our novel measures demonstrated attenuated practice effects, high test-retest reliabilities, equivalent alternate forms, and lack of ceiling effects. Moreover, we will also examine several biomarkers and markers that may increase risk for AD (e.g., APOE e4 carrier status, hippocampal atrophy and AD cortical thinning signature, family history of AD) in order to assess the sensitivity of the measures to these known biomarkers and so provide evidence for or against the validity of the cognitive and functional tests.